title: Molecular bases of chronic lymphocytic leukemia in light of new treatments.
abstract: The human genome era heralded a fundamental progress in the field of cancer genetics that shifted from a candidate gene approach toward global views of genomes and transcriptomes. Whole genome/exome sequencing has disclosed the genetic landscape of several hematologic tumors, providing comprehensive catalogs of somatic mutations and new insights into the genes that contribute to cellular transformation. Thanks to these technical progresses, research on the molecular pathogenesis of chronic lymphocytic leukemia (CLL) has also advanced at a sustained pace in recent times revealing NOTCH1, SF3B1, BIRC3, and MYD88 as the most recurrently (>5%) mutated genes that have been identified in CLL. Beside mutations of cancer related genes, another mechanism involved in disease initiation and progression of mature B-cell tumors, including CLL, is represented by B cell receptor (BCR) signaling. The BCR plays a central role in disease pathogenesis and, consequently, BCR signaling might represent a suitable target for therapy in many patients. Currently, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, which acts downstream the BCR signaling pathway, appears to be particularly promising and shows important clinical activity in CLL.
authors.affiliation: Division of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, 28100 Novara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.forename: Carmela
authors.initials: C
authors.lastname: Ciardullo
authors.forename: Valeria
authors.initials: V
authors.lastname: Spina
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002986:Clinical Trials as Topic; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009154:Mutation / Q000235:genetics; D010880:Piperidines; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D011947:Receptors, Antigen, B-Cell / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D011947:Receptors, Antigen, B-Cell; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine
keywords: Chronic lymphocytic leukemia; Genetics; Mutation; Treatment